The formation of sugar cataracts in laboratory animals has been observed to be initiated by aldose reductase catalyzed polyol synthesis and its accumulation in lens fibers and epithelium. It is now proposed to examine the implications of lens aldose reductase in the genesis of diabetic cataracts in higher animals and in persons having adult onset type of diabetes. Activities of various sugar metabolizing enzymes such as hexokinase, glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, polyol dehydrogenase as well as aldose reductase will be determined in dog, monkey, and human lenses. Any age variation will also be noted. In addition, the concentrations of cofactor nucleotides such as ATP, NAD, NADH, NADP, NADPH and creatine phosphate will be determined. The gross determination of enzymes and nucleotides will be supplemented by organ culture studies aimed at determining the significance of various factors in cellular dynamics. Studies will be continued to develop more potent inhibitors of aldose reductase and undertake their toxicological evaluation. The relationship that may exist between diabetic ametropia and aldose reductase will be examined with the help of the aldose reductase inhibitors and using biochemical, ophthalmologic and ultrasonographic techniques. Subsequently, studies on various aspects of the polyol pathway in lens will be extended to studies on retinal capillary mural cells derived by tissue culture.